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Journal of Immunology Research
Volume 2018 (2018), Article ID 7685371, 13 pages
https://doi.org/10.1155/2018/7685371
Research Article

Frequency of Interferon-Resistance Conferring Substitutions in Amino Acid Positions 70 and 91 of Core Protein of the Russian HCV 1b Isolates Analyzed in the T-Cell Epitopic Context

1Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia
2Russian Medical Academy of Continuous Professional Education, Moscow 125993, Russia
3Mechnikov Research Institute for Vaccines and Sera, Moscow 105064, Russia
4NF Gamaleja Research Center of Epidemiology and Microbiology, Moscow 123098, Russia
5Riga Stradins University, Riga LV-1007, Latvia

Correspondence should be addressed to V. S. Kichatova; ur.liam@avotahcik_arev and K. K. Kyuregyan; ur.xednay@naygeruyk-nerak

Received 29 August 2017; Accepted 29 November 2017; Published 7 February 2018

Academic Editor: Pedro A. Reche

Copyright © 2018 V. S. Kichatova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, ), but lower than that in the US HCV 1b strains (62.8%, ). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43.8%, ). Thus, a significant proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M substitution. In silico analysis of the epitopic structure of the regions of substitutions revealed that both harbor clusters of T-cell epitopes. Peptides encompassing these regions were predicted to bind to a panel of HLA class I molecules, with substitutions impairing peptide recognition by HLA I molecules of the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M substitutions may have evolved as the immune escape variants. Impairment of T-cell recognition may play a part in the negative effect of these substitutions on the response to IFN treatment.